tbuckley/cabot-search huggingface dataset:
Stratified care in hip arthroscopy: can we predict successful and unsuccessful outcomes? Development and external temporal validation of multivariable prediction models
Authors: Lasse Ishøi, Kristian Thorborg, Thomas Kallemose, Joanne L Kemp, Michael P Reiman, Mathias Fabricius Nielsen, Per Hölmich
Journal: British Journal of Sports Medicine (2023)

Objective Although hip arthroscopy is a widely adopted treatment option for hip-related pain, it is unknown whether preoperative clinical information can be used to assist surgical decision-making to avoid offering surgery to patients with limited potential for a successful outcome. We aimed to develop and validate clinical prediction models to identify patients more likely to have an unsuccessful or successful outcome 1 year post hip arthroscopy based on the patient acceptable symptom state. Methods Patient records were extracted from the Danish Hip Arthroscopy Registry (DHAR). A priori, 26 common clinical variables from DHAR were selected as prognostic factors, including demographics, radiographic parameters of hip morphology and self-reported measures. We used 1082 hip arthroscopy patients (surgery performed 25 April 2012 to 4 October 2017) to develop the clinical prediction models based on logistic regression analyses. The development models were internally validated using bootstrapping and shrinkage before temporal external validation was performed using 464 hip arthroscopy patients (surgery performed 5 October 2017 to 13 May 2019). Results The prediction model for unsuccessful outcomes showed best and acceptable predictive performance on the external validation dataset for all multiple imputations (Nagelkerke R 2 range: 0.25–0.26) and calibration (intercept range: −0.10 to −0.11; slope range: 1.06–1.09), and acceptable discrimination (area under the curve range: 0.76–0.77). The prediction model for successful outcomes did not calibrate well, while also showing poor discrimination. Conclusion Common clinical variables including demographics, radiographic parameters of hip morphology and self-reported measures were able to predict the probability of having an unsuccessful outcome 1 year after hip arthroscopy, while the model for successful outcome showed unacceptable accuracy. The externally validated prediction model can be used to support clinical evaluation and shared decision making by informing the orthopaedic surgeon and patient about the risk of an unsuccessful outcome, and thus when surgery may not be appropriate.
Efficacy and safety of enhanced recovery after surgery protocol on minimally invasive bariatric surgery: a meta-analysis
Authors: Benjian Gao, Jianfei Chen, Yongfa Liu, Shuai Hu, Rui Wang, Fangyi Peng, Chen Fang, Yu Gan, Song Su, Yunwei Han, Xiaoli Yang, Bo Li
Journal: International Journal of Surgery (2023)

Enhanced recovery after surgery (ERAS), a multidisciplinary and multimodal perioperative care protocol, has been widely used in several surgical fields. However, the effect of this care protocol on patients receiving minimally invasive bariatric surgery remains unclear. This meta-analysis compared the clinical outcomes of the ERAS protocol and standard care (SC) in patients who underwent minimally invasive bariatric surgery.PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched to identify literature reporting the effects of the ERAS protocol on clinical outcomes in patients undergoing minimally invasive bariatric surgery. All the articles published until 01 October 2022, were searched, followed by data extraction of the included literature and independent quality assessment. Then, pooled mean difference (MD) and odds ratio with a 95% CI were calculated by either a random-effects or fixed-effects model.Overall, 21 studies involving 10 764 patients were included in the final analysis. With the ERAS protocol, the length of hospitalization (MD: -1.02, 95% CI: -1.41 to -0.64, P <0.00001), hospitalization costs (MD: -678.50, 95% CI: -1196.39 to -160.60, P =0.01), and the incidence of 30-day readmission (odds ratio =0.78, 95% CI: 0.63-0.97, P =0.02) were significantly reduced. The incidences of overall complications, major complications (Clavien-Dindo grade ≥3), postoperative nausea and vomiting, intra-abdominal bleeding, anastomotic leak, incisional infection, reoperation, and mortality did not differ significantly between the ERAS and SC groups.The current meta-analysis indicated that the ERAS protocol could be safely and feasibly implemented in the perioperative management of patients receiving minimally invasive bariatric surgery. Compared with SC, this protocol leads to significantly shorter hospitalization lengths, lower 30-day readmission rate, and hospitalization costs. However, no differences were observed in postoperative complications and mortality.
Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS)
Authors: Antonio Torrelo, Barbara Rewerska, Maria Galimberti, Amy Paller, Chin-Yi Yang, Apurva Prakash, Danting Zhu, Marco Antonio G Pontes Filho, Wen-Shuo Wu, Lawrence F Eichenfield
Journal: British Journal of Dermatology (2023)

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved in many countries for moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.To evaluate the efficacy and safety of three doses of baricitinib in combination with low-to-moderate potency topical corticosteroids in paediatric patients with moderate-to-severe AD.Patients (aged 2 to < 18 years) were randomized (1 : 1 : 1 : 1) to once-daily baricitinib low dose (1 mg equivalent), medium dose (2 mg equivalent), high dose (4 mg equivalent) or placebo for 16 weeks. The primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment® (vIGA-AD) of 0/1 with a ≥ 2-point improvement at week 16. Key secondary endpoints included the proportions of patients achieving ≥ 75% and ≥ 90% improvement in the Eczema Area and Severity Index (EASI-75 and EASI-90, respectively), ≥ 75% improvement in the SCORing Atopic Dermatitis (SCORAD 75), mean change from baseline in EASI score and proportion of patients achieving a 4-point improvement in the Itch Numeric Rating scale (NRS) for patients aged ≥ 10 years. Primary and key secondary efficacy analyses were conducted on the intent-to-treat population and adjusted for multiplicity. Safety analyses included all randomized patients who received ≥ 1 dose of study treatment.A total of 483 patients were randomized (mean age 12 years). The baricitinib 4 mg equivalent achieved a statistically significant (P < 0.05) improvement vs. placebo on all 16-week endpoints (vIGA 0/1 with ≥ 2-point improvement, EASI-75, EASI-90, SCORAD 75, mean change in EASI score and Itch NRS 4-point improvement for patients aged ≥ 10 years). Improvement (P < 0.05, non-multiplicity adjusted) was also observed for baricitinib 4 mg equivalent vs. placebo in the ability to fall asleep and in reduction of topical corticosteroid use. Few patients discontinued due to adverse events (1.6% for placebo and 0.6% for those treated with baricitinib). There were no deaths, venous thromboembolic events, arterial thrombotic events, major adverse cardiovascular events, malignancies, gastrointestinal perforations or opportunistic infections seen.The results indicate that baricitinib offers a potential therapeutic option with a favourable benefit-risk profile for paediatric patients with moderate-to-severe AD who are candidates for systemic therapies.
Unusual Surface Coagulation Activation Patterns of Crystalline and Amorphous Silicate‐Based Biominerals
Authors: Chunyu Liu, Xu Cui, Yunbo Du, Xue Wang, Jua Kim, Shuaijie Li, Liyan Zhang, Xiaoli Zhao, Limin Zhao, Pengfei Tian, Hao Zhang, Kun Su, Xian Li, Haobo Pan
Journal: Advanced Healthcare Materials (2023)

Abstract Activation of coagulation cascades, especially FX and prothrombin, prevents blood loss and reduces mortality from hemorrhagic shock. Inorganic salts are efficient but cannot stop bleeding completely in hemorrhagic events, and rebleeding carries a significant mortality risk. The coagulation mechanism of biominerals has been oversimplified in the past two decades, limiting the creation of novel hemostats. Herein, at the interface, the affinity of proteins, the protease activity, fibrinolysis, hydration shell, and dynamic microenvironment are monitored at the protein level. Proteomic analysis reveals that fibrinogen and antithrombin III's affinity for kaolin's interface causes a weak thrombus and rebleeding during hemostasis. Inspiringly, amorphous bioactive glass (BG) with a transient‐dynamic ion microenvironment breaches the hydration layer barrier and selectively and slightly captures procoagulant components of kiniogen‐1, plasma kallikrein, FXII, and FXI proteins on its interface, concurrently generating a continuous biocatalytic interface to rapidly activate both intrinsic and extrinsic coagulation pathways. Thus, prothrombin complexes are successfully hydrolyzed to thrombin without platelet membrane involvement, speeding production of high‐strength clots. This study investigates how the interface of inorganic salts assists in coagulation cascades from a more comprehensive micro‐perspective that may help elucidate the clinical application issues of kaolin‐gauze and pave the way to new materials for managing hemorrhage.
A 211At-labelled mGluR1 inhibitor induces cancer senescence to elicit long-lasting anti-tumor efficacy
Authors: Lin Xie, Lulu Zhang, Kuan Hu, Masayuki Hanyu, Yiding Zhang, Masayuki Fujinaga, Katsuyuki Minegishi, Takayuki Ohkubo, Kotaro Nagatsu, Cuiping Jiang, Takashi Shimokawa, Kazuma Ashisuke, Noriyuki Okonogi, Shigeru Yamada, Feng Wang, Rui Wang, Ming-Rong Zhang
Journal: Cell Reports Medicine (2023)

Metabotropic glutamate receptor 1 (mGluR1), a key mediator of glutamatergic signaling, is frequently overexpressed in tumor cells and is an attractive drug target for most cancers. Here, we present a targeted radiopharmaceutical therapy strategy that antagonistically recognizes mGluR1 and eradicates mGluR1+ human tumors by harnessing a small-molecule alpha (α)-emitting radiopharmaceutical, 211At-AITM. A single dose of 211At-AITM (2.96 MBq) in mGluR1+ cancers exhibits long-lasting in vivo antitumor efficacy across seven subtypes of four of the most common tumors, namely, breast cancer, pancreatic cancer, melanoma, and colon cancers, with little toxicity. Moreover, complete regression of mGluR1+ breast cancer and pancreatic cancer is observed in approximate 50% of tumor-bearing mice. Mechanistically, the functions of 211At-AITM are uncovered in downregulating mGluR1 oncoprotein and inducing senescence of tumor cells with a reprogrammed senescence-associated secretory phenotype. Our findings suggest α-radiopharmaceutical therapy with 211At-AITM can be a useful strategy for mGluR1+ pan-cancers, regardless of their tissue of origin.
Mixed-donor faecal microbiota transplantation was associated with increased butyrate-producing bacteria for obesity
Authors: Zhilu Xu, Joyce Wing Yan Mak, Yu Lin, Keli Yang, Qin Liu, Fen Zhang, Louis Lau, Whitney Tang, Jessica YL Ching, Hein M Tun, Paul Chan, Francis K L Chan, Siew C Ng
Journal: Gut (2023)
Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors
Authors: Fiore Cattaruzza, Ayesha Nazeer, Milton To, Mikhail Hammond, Caitlin Koski, Lucas Y. Liu, V. Pete Yeung, Deena A. Rennerfeldt, Angela Henkensiefken, Michael Fox, Sharon Lam, Kari M. Morrissey, Zachary Lange, Vladimir N. Podust, Mika K. Derynck, Bryan A. Irving, Volker Schellenberger
Journal: Nature Cancer (2023)

To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank the N and C termini of the TCE and are designed to be released by proteases in the tumor microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with XTEN polypeptide masking providing up to 4-log-fold protection. In vivo, HER2-XPAT protein induces protease-dependent antitumor activity and is proteolytically stable in healthy tissues. In non-human primates, HER2-XPAT protein demonstrates a strong safety margin (>400-fold increase in tolerated maximum concentration versus uTCE). HER2-XPAT protein cleavage is low and similar in plasma samples from healthy and diseased humans and non-human primates, supporting translatability of stability to patients. EGFR-XPAT protein confirmed the utility of XPAT technology for tumor targets more widely expressed in healthy tissues.
The three-dimensional weakly supervised deep learning algorithm for traumatic splenic injury detection and sequential localization: an experimental study
Authors: Chi-Tung Cheng, Hou-Shian Lin, Chih-Po Hsu, Huan-Wu Chen, Jen-Fu Huang, Chih-Yuan Fu, Chi-Hsun Hsieh, Chun-Nan Yeh, I-Fang Chung, Chien-Hung Liao
Journal: International Journal of Surgery (2023)

Splenic injury is the most common solid visceral injury in blunt abdominal trauma, and high-resolution abdominal computed tomography (CT) can adequately detect the injury. However, these lethal injuries sometimes have been overlooked in current practice. Deep learning (DL) algorithms have proven their capabilities in detecting abnormal findings in medical images. The aim of this study is to develop a three-dimensional, weakly supervised DL algorithm for detecting splenic injury on abdominal CT using a sequential localization and classification approach.The dataset was collected in a tertiary trauma center on 600 patients who underwent abdominal CT between 2008 and 2018, half of whom had splenic injuries. The images were split into development and test datasets at a 4 : 1 ratio. A two-step DL algorithm, including localization and classification models, was constructed to identify the splenic injury. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Grad-CAM (Gradient-weighted Class Activation Mapping) heatmaps from the test set were visually assessed. To validate the algorithm, we also collected images from another hospital to serve as external validation data.A total of 480 patients, 50% of whom had spleen injuries, were included in the development dataset, and the rest were included in the test dataset. All patients underwent contrast-enhanced abdominal CT in the emergency room. The automatic two-step EfficientNet model detected splenic injury with an AUROC of 0.901 (95% CI: 0.836-0.953). At the maximum Youden index, the accuracy, sensitivity, specificity, PPV, and NPV were 0.88, 0.81, 0.92, 0.91, and 0.83, respectively. The heatmap identified 96.3% of splenic injury sites in true positive cases. The algorithm achieved a sensitivity of 0.92 for detecting trauma in the external validation cohort, with an acceptable accuracy of 0.80.The DL model can identify splenic injury on CT, and further application in trauma scenarios is possible.
Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity
Authors: Yingqi Liu, Yang Fei, Xuan Wang, Bingbing Yang, Menghuan Li, Zhong Luo
Journal: Molecular Therapy (2023)

cGAS-STING signaling is a central component in the therapeutic action of most existing cancer therapies. The accumulated knowledge of tumor immunoregulatory network in recent years has spurred the development of cGAS-STING agonists for tumor treatment as an effective immunotherapeutic strategy. However, the clinical translation of these agonists is thus far unsatisfactory because of the low immunostimulatory efficacy and unrestricted side effects under clinically relevant conditions. Interestingly, the rational integration of biomaterial technology offers a promising approach to overcome these limitations for more effective and safer cGAS-STING-mediated tumor therapy. Herein, we first outline the cGAS-STING signaling axis and generally discuss its association with tumors. We then symmetrically summarize the recent progress in those biomaterial-based cGAS-STING agonism strategies to generate robust antitumor immunity, categorized by the chemical nature of those cGAS-STING stimulants and carrier substrates. Finally, a perspective is provided to discuss the existing challenges and potential opportunities in cGAS-STING modulation for tumor therapy.
Neural Control of Sexually Dimorphic Social Behavior: Connecting Development to Adulthood
Authors: Margaret M. McCarthy
Journal: Annual Review of Neuroscience (2023)

Rapid advances in the neural control of social behavior highlight the role of interconnected nodes engaged in differential information processing to generate behavior. Many innate social behaviors are essential to reproductive fitness and therefore fundamentally different in males and females. Programming these differences occurs early in development in mammals, following gonadal differentiation and copious androgen production by the fetal testis during a critical period. Early-life programming of social behavior and its adult manifestation are separate but yoked processes, yet how they are linked is unknown. This review seeks to highlight that gap by identifying four core mechanisms (epigenetics, cell death, circuit formation, and adult hormonal modulation) that could connect developmental changes to the adult behaviors of mating and aggression. We further propose that a unique social behavior, adolescent play, bridges the preweaning to the postpubertal brain by engaging the same neural networks underpinning adult reproductive and aggressive behaviors.
Membrane phospholipid remodeling modulates nonalcoholic steatohepatitis progression by regulating mitochondrial homeostasis
Authors: Ye Tian, Matthew J. Jellinek, Kritika Mehta, Sun Mi Seok, Shanny H. Kuo, Wei Lu, Ruicheng Shi, Richard Lee, Gee W. Lau, Jongsook Kim Kemper, Kai Zhang, David A. Ford, Bo Wang
Journal: Hepatology (2023)

Background and Aims: NASH, characterized by inflammation and fibrosis, is emerging as a leading etiology of HCC. Lipidomics analyses in the liver have shown that the levels of polyunsaturated phosphatidylcholine (PC) are decreased in patients with NASH, but the roles of membrane PC composition in the pathogenesis of NASH have not been investigated. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), a phospholipid (PL) remodeling enzyme that produces polyunsaturated PLs, is a major determinant of membrane PC content in the liver. Approach and Results: The expression of LPCAT3 and the correlation between its expression and NASH severity were analyzed in human patient samples. We examined the effect of Lpcat3 deficiency on NASH progression using Lpcat3 liver-specific knockout (LKO) mice. RNA sequencing, lipidomics, and metabolomics were performed in liver samples. Primary hepatocytes and hepatic cell lines were used for in vitro analyses. We showed that LPCAT3 was dramatically suppressed in human NASH livers, and its expression was inversely correlated with NAFLD activity score and fibrosis stage. Loss of Lpcat3 in mouse liver promotes both spontaneous and diet-induced NASH/HCC. Mechanistically, Lpcat3 deficiency enhances reactive oxygen species production due to impaired mitochondrial homeostasis. Loss of Lpcat3 increases inner mitochondrial membrane PL saturation and elevates stress-induced autophagy, resulting in reduced mitochondrial content and increased fragmentation. Furthermore, overexpression of Lpcat3 in the liver ameliorates inflammation and fibrosis of NASH. Conclusions: These results demonstrate that membrane PL composition modulates the progression of NASH and that manipulating LPCAT3 expression could be an effective therapeutic for NASH.
MY‐1‐Loaded Nano‐Hydroxyapatite Accelerated Bone Regeneration by Increasing Type III Collagen Deposition in Early‐Stage ECM via a Hsp47‐Dependent Mechanism
Authors: Zhang Yanli, Mo Jiayao, Zheng Chunqing, Zeng Yuting, Zhou Zhiyan, Zhang Yulin, Li Minghan, Shao Longquan, Yang Dehong, Yan Wenjuan
Journal: Advanced Healthcare Materials (2023)

The extracellular matrix (ECM) plays a crucial part in regulating stem cell function through its distinctive mechanical and chemical effect. Therefore, it is worth studying how to activate the driving force of osteoblast cells by dynamic changing of ECM and accelerate the bone regeneration. In this research, a novel peptide MY-1 is designed and synthesized. To achieve its sustained releasing, the nano-hydroxyapatite (nHA) is chosen as the carrier of MY-1 by mixed adsorption. The results reveal that the sustainable releasing of MY-1 regulates the synthesis and secretion of ECM from rat bone marrow mesenchymal stem cells (rBMSCs), which promotes the cell migration and osteogenic differentiation in the early stage of bone regeneration. Further analyses demonstrate that MY-1 increases the expression and nuclear translocation of β-catenin, and then upregulates the level of heat shock protein 47 (Hsp47), thereby accelerating the synthesis and secretion of type III collagen (Col III) at the early stage. Finally, the promoted rapid transformation of Col III to Col I at late stage benefits the bone regeneration. Hence, this study can provide a theoretical basis for the local application of MY-1 in bone regeneration.
Cholecystectomy and risk of liver disease: a systematic review and meta-analysis of 27 million individuals
Authors: De Luo, Xin-Pei Chen, Yang Dai, Fei Kuang, Mao-Ji Kang, Bo Li, Song Su
Journal: International Journal of Surgery (2023)

Background: There is still a lack of knowledge on the association between cholecystectomy and liver disease. This study was conducted to summarize the available evidence on the association of cholecystectomy with liver disease and quantify the magnitude of the risk of liver disease after cholecystectomy. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched systematically from database inception to January 2023 to identify eligible studies that evaluated the association between cholecystectomy and the risk of liver disease. Meta-analysis was conducted to obtain a summary odds ratio (OR) and 95% confidence interval (CI) using a random-effects model. Results: We identified 20 studies with a total of 27 320 709 individuals and 282 670 liver disease cases. Cholecystectomy was associated with an increased risk of liver disease (OR: 1.63, 95% CI: 1.34–1.98). In particular, cholecystectomy was found to be significantly associated with a 54% increased risk of nonalcoholic fatty liver disease (OR: 1.54, 95% CI: 1.18–2.01), a 173% increased risk of cirrhosis (OR: 2.73, 95% CI: 1.81–4.12), and a 46% increased risk of primary liver cancer (OR: 1.46, 95% CI: 1.18–1.82). Conclusions: There is an association between cholecystectomy and the risk of liver disease. Our results suggest that strict surgical indications should be implemented to reduce unnecessary cholecystectomy. Additionally, the routine assessment of liver disease is necessary for patients with a history of cholecystectomy. More prospective large-sample studies are required for better estimates of the risk.